Synthesis and in vitro antimalarial activity of tetraoxane-amine/amide conjugates

• Published in: European journal of medicinal chemistry 2011-07, Vol.46 (7), p.2816-2827
• Main Authors: Kumar, Nitin, Khan, Shabana I., Atheaya, Himanshu, Mamgain, Ritu, Rawat, Diwan S.
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Amine conjugates; Amines - chemistry; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - pharmacology; Antiparasitic agents; Artemisinin; Artemisinins - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cercopithecus aethiops; Chloroquine - pharmacology; Dose-Response Relationship, Drug; Drug Design; Drug Resistance; Humans; Inhibitory Concentration 50; Medical sciences; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Structure-Activity Relationship; Tetraoxane; Tetraoxanes - chemical synthesis; Tetraoxanes - pharmacology; Vero Cells
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.04.002

A series of tetraoxanes, tetraoxane-amine and tetraoxane-amide conjugates have been synthesized and screened for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Most of the conjugates showed slightly better antimalarial activity than the parent tetraoxanes. Three of the conjugate compounds were potentially active with IC 50 values in the range of 0.38–0.80 μM. Cytotoxicity of four selected compounds was also evaluated in a panel of four cancer (SK-MEL, KB, BT-549, SK-OV-3) and two non-cancer (Vero and LLC-PK 11) cell lines up to a concentration of 25 μM and none of the compounds was found toxic to any of the cells. Total 74 tetraoxanes, tetraoxane-Schiff base, tetraoxane-amine and tetraoxane-amide conjugates have been synthesized and screened for in vitro antimalarial activity against D6 and W2 strains of Plasmodium falciparum. Most of the conjugates showed slightly better antimalarial activity than the parent tetraoxanes, and three of the hybrid compounds were potentially active. [Display omitted] ► Synthesis and antimalarial activity of tetraoxane-amine and tetraoxane-amide conjugates have been reported. ► Antimalarial activity against D6 and W2 strains of P. falciparum showed slightly better activity than the parent tetraoxanes. ► Three of the hybrids were potentially active and did not show any cytotoxicity against panel of four cancer and two non-cancer cell lines.